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University of Utah Medical School Researchers Receive Nearly $3 Million in Grants to Study Diabetes Complications

Oct. 9, 2006 — A protein that promotes nerve and blood vessel growth will be tested in mice as part of $2.7 million in grants University of Utah School of Medicine researchers just received to study diabetes.

By spurring blood vessel and nerve growth, the protein, Netrin-1, potentially could prevent or reverse devastating complications of diabetes related to impaired circulation, such as limb loss, blindness, and cardiovascular disease.

The grants, two from the Juvenile Diabetes Research Foundation (JDRF) and one from the National Institutes of Health (NIH), also will fund wider research into the cardiovascular complications of diabetes in mice models, including how the disease affects mitochondria, a key component in cells the body uses to convert glucose and fatty acids into energy for the heart. Heart disease is the most common cause of death among the nearly 21 million Americans with type 1 or type 2 diabetes.

University of Utah endocrinologist E. Dale Abel, M.D., Ph.D., associate professor of internal medicine and an investigator with the University’s Program in Human Molecular Biology and Genetics, is principal investigator on the grants

The JDRF, whose mission is to find a cure for type 1 diabetes, awarded the University $800,000 for type 1 diabetes research. Each of the two grants totals about $400,000 a year for two years.

According to Dr. Helen Nickerson, Scientific Program Manager for JDRF, “People with type 1 diabetes live with the constant threat of developing such devastating complications as neuropathy, nephrology, retinopathy and cardiovascular disease. JDRF takes the responsibility of preventing these complications very seriously. Dr Abel’s studies with netrin and mitochondria are highly innovative, with the potential to reveal novel pathways of damage and targets for therapy, and we are glad to support the promising work being done by Dr. Abel and his team at the University of Utah.”

The NIH grant provides $373,750 a year for five years, a $1.9 million total. The research will draw on the University’s interdisciplinary approach to unraveling problems of medical science, according to Abel.

Type 1 diabetes is an autoimmune disease almost always diagnosed in people age 30 and younger, many of whom are children. It’s estimated that type 1 accounts for up to 10 percent of diabetes cases in the United States. Researchers don’t know what causes this devastating type of diabetes, in which the pancreas makes little or no insulin. Insulin is the hormone that helps glucose enter cells to be converted to energy for the body.

When glucose builds in the blood, it causes hunger, excessive urination, and thirst. Many people with type 1 diabetes take insulin shots or oral medication to help control complications of the disease.

Type 2 diabetes is a metabolic disorder linked to diet, obesity, and other factors. Changing and “supersized” diets have caused the incidence of this type of diabetes to increase sharply in the United States and around the world. As the economies of developing countries, such as India and China, grow, the incidence of type 2 diabetes is expected to soar as people consume more calories in less healthy foods.

“There has been progress in understanding both types of diabetes,” Abel said. “But we have a long way to go.”

Cardiologists Sheldon E. Litwin, M.D., professor of internal medicine, and Dean Y. Li, M.D., Ph.D., associate professor of internal medicine who’s also with the Human Molecular Biology and Genetics program, are co-investigators on the grants.

In recent work, Li has shown Netrin-1 promotes blood vessel growth (angiogenesis) and nerve growth in laboratory cultures and mice. The two-year JDRF novel therapeutics grant will focus on a trial of Netrin-1 in genetically diverse mice with type 1 diabetes, rather than those bred to be genetically identical in laboratories.

If the protein promotes angiogenesis and nerve growth in two genetically random lines of mice, it could be a major step in showing the therapy’s broader applications and in taking it to clinical trials, according to Abel. The U of U group will partner with University of Michigan researchers on this study.

With a second JDRF grant, aimed at fostering innovative research partnerships, University researchers are joining with Utah State University to analyze how diabetes affects mitochondria. The Center for Integrated Biosystems-a premier laboratory at Utah State headed by Bart Weimer-will employ a technique called proteomics and mass spectroscopy to analyze fragments of mitochondrial proteins to identify alterations that occur in diabetes.

“If we find a protein that’s specifically altered, we may be able to identify a target that could then be used to reverse certain diabetic complications,” Abel said.

The NIH grant is the second round of a program started five years ago, which established a consortium of universities using animal models to study the complications of diabetes. Abel was a co-principal investigator on a $2.5 million grant awarded to the University through this program in 2001.

Abel will use the latest NIH grant to study mouse models with cardiovascular disease and look for ways of reducing diabetes-caused heart failure and ischemic heart disease. He’ll also research potentials for even reversing the effects of small vessel disease that lead to the ravaging complications of diabetes.